Recurrence Score Results Research Articles

Use of 21-gene recurrence score assay to individualize adjuvant chemotherapy recommendations in ER+/HER2\u2212 node positive breast cancer\u2014A National Cancer Database study

The 21-gene Recurrence Score (RS) assay is prognostic and predictive of adjuvant chemotherapy benefit in node positive (N+) breast cancer (BC). We sought to evaluate use patterns of RS assay in N+, ER+/HER2− BC and the impact of RS on recommendations for adjuvant chemotherapy. Patients with T1-T4c,N1mi-N3, ER+/HER2− BC diagnosed 2010–2013 in the National Cancer Database were analyzed. Multivariable logistic regression assessed factors influencing RS testing and chemotherapy recommendations based on RS. Among 72,897 patients, RS was obtained in 20.6%, increasing from 15.0% in 2010 to 24.5% in 2013 (p < 0.001). RS testing was most common in N1mi (43.7%) followed by N1 (22.1%) and rare in N2/N3 (3.3%). Of the 12,536 with quantitative RS results, 61.1% were low RS, 32.3% intermediate RS and 6.6% high RS. Chemotherapy was recommended less frequently in patients with RS testing (50.4%) vs. those not tested (81.0%, p < 0.001). In N1mi/N1 patients, chemotherapy recommendation varied by RS; however, in N2/N3 patients, chemotherapy was recommended in the majority (70.9–87.5%) regardless of RS. Most patients (>85%) with RS ≥ 26 were recommended chemotherapy regardless of nodal stage. For patients with RS < 26, chemotherapy recommendations increased with higher N and T stage, grade, and younger age (p < 0.001). Histology was not associated with chemotherapy recommendation in any RS subset. The RS assay is frequently and increasingly being used for decision making in node positive ER+/HER2− breast cancer patients and its use is associated with lower rates of adjuvant chemotherapy.

Distribution of 21-Gene Recurrence Scores among Breast Cancer Histologic Subtypes

Context.— The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain. Objective.— To determine the distribution of RS among various histologic subtypes using a population database. Design.— Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database. Recurrence scores were categorized into risk groups using both traditional and Trial Assigning Individualized Options for Treatment cutoffs. Multivariable logistic regression was used to determine factors associated with high-risk RS. Results.— We identified 45 618 patients with stage I to III, estrogen receptor–positive, HER2-negative breast cancer who had RS available. Overall, 3087 (7%) and 6337 (14%) of cancers were class...

187P - Summary of head-to-head comparisons of patient (pt) risk classifications by the 21-gene recurrence score (RS) assay and other genomic assays for early breast cancer (EBC)

Background: Many genomic assays that assess recurrence risk in EBC are prognostic, but they differ in risk group stratification, which can affect clinical utility. Prospective outcomes of > 50K pts treated based on 21-gene RS results have shown that pts with low RS EBC can safely forgo chemotherapy. Because of its extensive validation and wide clinical use, the RS assay is a common comparator in head-to-head studies with other assays. Methods: Published/presented studies of the RS assay performed on same tumor samples with Breast Cancer Index (BCI), EndoPredict (EP) or EP+clinical features (EPclin), MammaPrint (MMP), and/or Prosigna (ROR) assays were reviewed. Study findings were summarized descriptively. Results: 14 studies were found that compared the RS assay with BCI (1), BCI, EPclin, and ROR (1), EP/EPclin (2), MMP (6), and ROR (4). Overall discordance in risk stratification ranged from 43% to 66% between assays (Table). The RS assay classifies 12% of pts as high risk, compared with EP (63%), EPclin (48%), and MMP (46%), assays with low/high risk groups, and compared with BCI (16%) and ROR (33%), assays that, like the RS assay, use three risk groups.Table187PDiscordancea Between the RS Assay and Other AssaysBCIROREP/EPclinMMPStudyb1-level2-levelOverall1-level2-levelOverall1-level2-levelOverall1-level2-levelOverallSestak 201637%5%42%Bartlett 2016c40%10%50%Alvarado 201537%10%46%Dowsett 201341%3%43%Sinn 201745%20%66%Varga 201329%/29%18%/21%47%/50%Clough 201338%19%57%Denduluri 201134%25%58%Maroun 201531%22%53%Shivers 201326%19%44%a. Overall=any discordance in risk classification between the RS assay and other; 1-level=discordance of one risk category (low ↔ intermediate or intermediate ↔ high); 2-level=discordance of two risk categories (low ↔ high). b. Four studies lacked risk classification information appropriate for inclusion in this table. c. Study used nonstandard RS cutoffs for the RS vs. MMP comparison. Open table in a new tab a. Overall=any discordance in risk classification between the RS assay and other; 1-level=discordance of one risk category (low ↔ intermediate or intermediate ↔ high); 2-level=discordance of two risk categories (low ↔ high). b. Four studies lacked risk classification information appropriate for inclusion in this table. c. Study used nonstandard RS cutoffs for the RS vs. MMP comparison. Conclusions: The five most common genomic assays in clinical use for EBC risk-stratify pts differently and thus are not interchangeable. Of these, the RS assay classifies the smallest proportion of pts as high risk. Legal entity responsible for the study: Zsuzsanna Varga Funding: Genomic Health Disclosure: Z. Varga: Consultant/advisor: Genomic Health, Roche. P. Sinn: Advisor: Genomic Health. D. McCullough, A. Lau, M.C. Stöppler, F.L. Baehner, C. Chao: Employment and stock ownership: Genomic Health. A. Seidman: Consultant/speaker: Genomic Health.

Effect of 21-gene recurrence score on chemotherapy decisions for patients with estrogen receptor-positive, epidermal growth factor receptor 2-negative and lymph node-negative early stage-breast cancer

Objective: To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer. Methods: One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed. Results: After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy. Conclusion: Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer.

The 21-gene recurrence score in special histologic subtypes of breast cancer with favorable prognosis.

The 21-gene recurrence score (RS) assay predicts the likelihood of distant recurrence and chemotherapy benefit in early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. Data on the RS of special histologic subtypes of invasive breast carcinoma with favorable prognosis are limited. We reviewed our institutional database to identify patients with special histologic subtypes of breast cancer associated with favorable prognosis and available RS results. Our cohort consists of fifty-seven women: thirty-three patients with pure mucinous carcinoma (MC), ten with tubular carcinoma (TC), nine with encapsulated papillary carcinoma (EPC), and five with solid papillary carcinoma (SPC). Most (44/57, 77.2%) carcinomas had low RS (≤17), and none had high RS (≥31). All EPCs had low RS, but other subtypes had RS 18-30. Higher RS was associated with lower progesterone receptor (PR) expression by immunohistochemistry and lower PR mRNA scores (P≤0.007). No morphologic feature (tumor grade, biopsy site changes, cellular stroma, inflammatory cells) was associated with RS≥18. At a median follow-up of 40months, the distant recurrence-free survival was 100%. One patient with SPC developed locoregional recurrence at 22months. As the largest series to date, our study raises the question of whether the RS assay is necessary for breast cancers with favorable histology. Reflex testing of node-negative, ER+/HER2- breast cancers may be deferred for these special histologic subtypes, emphasizing the need for multidisciplinary discussions between breast pathologists and other members of the breast cancer team.

SEER study of breast cancer specific mortality (BCSM) in patients with lobular tumors treated based on recurrence score results.

11568 Background: Linking the 21-gene assay RS result to the SEER Registries demonstrated very low 5-y BCSM with low RS and high 5-y BCSM with high RS across subgroups, such as nodal status, age, tumor size and grade (npj Breast Cancer 2016). Given the large sample size and interest in outcomes as a function of tumor characteristics, we characterized the relationship between RS results and BCSM in patients reported by SEER with lobular morphology. Methods: Patients with RS and lobular morphology based on the registry ICD-O-3 code 8520 were eligible if node negative (N0) or node positive up to 3 positive nodes (N+mic,1-3), HR+, HER2- negative, no prior malignancy, and diagnosed between Jan 2004 and Dec 2012. No information in SEER is available regarding lobulars, ie., trabecular, alveolar, solid and pleomorphic. 5-y BCSM was estimated using actuarial methods. Results: There were 6,075 eligible patients reported with lobular morphology (11% of cases). Median age was 59 years; 88%/12% were N0/N+; 31%/62%/7% grade 1/2/3; 61%/39% ≤2 cm/&gt;2 cm. Median follow-up was 44 months. A minority (8%) had RS &gt;25. Chemotherapy (CT) use and BCSM increased with increasing RS. In multivariable analysis in N0 disease, continuous RS result and tumor size predicted BCSM (p=0.003 and p=0.04, respectively), whereas age and tumor grade were non-significant. In multivariable analysis in N+ disease, continuous RS result alone predicted BCSM (p=0.002). Conclusions: In these analyses the prognosis of patients with lobular breast cancer treated based on RS results depends on both nodal status and the RS result. The 5-y BCSM for lobular breast cancer is excellent with RS of 25 or less, and increases for RS &gt;25. [Table: see text]

Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma (RCC): Validation of the 16-gene Recurrence Score in stage III patients.

4508 Background: Adjuvant therapy with sunitinib (SU) compared with placebo (PBO) prolonged disease-free survival (DFS) in 615 patients (pts) with high-risk RCC (hazard ratio [HR] 0.76; P= 0.03) in the S-TRAC trial. The 16-gene Recurrence Score (RS) was developed and validated to predict risk of recurrence of RCC after nephrectomy in 2 cohorts of stage I–III pts (Rini et al., Lancet Oncol 2015;16:676-85). We present further validation of RS results in high-risk stage III pts from S-TRAC. Methods: The study was prospectively designed with prespecified genes, algorithm, endpoints, analytical methods, and analysis plan using primary RCC tissues from 212 evaluable pts with informed consent. Gene expression was quantitated by RT-PCR; primary analysis focused on stage III (n = 193 pts). Time to recurrence (TTR) and DFS were analyzed using Cox proportional hazard regression. Results: Baseline characteristics were similar in SU and PBO arms and in pts with and without gene expression data; effect of SU was numerically similar to that in the entire trial (DFS HR 0.78, 95% CI 0.48–1.24; P= 0.29). RS predicted TTR and DFS in both treatment arms with the strongest results observed in PBO arm where high RS group had significantly higher risk (Table). Interaction of RS with treatment was not significant (TTR P= 0.192; DFS P= 0.219); however, the number of events was relatively low. Conclusions: The prognostic value of the 16-gene assay was confirmed in S-TRAC. RS is now validated with consistent results in 2 separate studies (level IB evidence). RS results may help identify patients at high risk who could derive higher absolute benefit from adjuvant treatment. The predictive value of RS to select patients for adjuvant SU requires further investigation in independent adjuvant trials. [Table: see text]

Treatments/clinical outcomes in ER+ HER2-negative breast cancer (BC) where treatment decisions were recurrence score (RS)-guided: Analysis by histologic subtype.

e12053 Background: The RS assay is widely used to guide treatment decisions in ER+ HER2-negative early BC regardless of tumor histology. However, the RS validation studies did not include an analysis by histologic subtype. We investigated treatments/clinical outcomes in RS-tested Clalit Health Services (CHS) patients (pts) by histologic subtype, focusing on invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Methods: This exploratory analysis of the CHS cohort included BC pts with N0/N1mi/N1 disease who were RS-tested from 1/2006 through 12/2010 (N0) or 12/2011 (N1mi/N1). Data from medical records were analyzed to assess risks of distant recurrence and BC death by histologic subtype. Results: The cohort included 2510 pts: 2060 (82%) IDC, 298 (12%) ILC, and 152 (6%) unknown/others. Median follow up for IDC/ILC pts was 6.0/6.1 yrs. Median age in IDC/ILC pts was 60/62 yrs; median tumor size was 1.5/1.8 cm; 71%/71% were N0, and 29%/29% were N1mi/N1. RS distribution (&lt;18, 18-30, ≥31) was 50%, 39%, and 11%, respectively for IDC pts and 48%, 48%, and 4%, respectively, for ILC pts. Chemotherapy (CT) use for each RS group was similar between IDC and ILC pts; 5-yr Kaplan-Meier estimates for the risk of distant recurrence and BC death differed significantly across RS groups in both IDC and ILC; clinical outcomes for IDC and ILC pts were similar within risk groups see Table. Conclusions: For both IDC and ILC pts, treatment was aligned with the RS results. Within each RS group, there was no difference in clinical outcomes between these histologic subtypes, however the number of pts with ILC and RS≥31 was limited. [Table: see text]

The performance of the 21-gene assay standard cutpoints of 18 and 31 in HR+, HER2- invasive breast cancer (BC), while waiting for TAILORx mid-range recurrence score results.

537 Background: The Recurrence Score (RS) was shown in NSABP B-20 to predict chemotherapy (CT) benefit for RS ≥31 and no CT benefit for RS &lt;18. The TAILORx results for RS &lt;11 (NEJM 2015) reported excellent outcomes with no opportunity for CT to add additional benefit. As we await TAILORx results for RS 11-25, we characterized BC specific mortality (BCSM) for RS groups (cutoffs of 11, 18, 25, and 31) in the population-based SEER study of pts treated based on RS. Methods: RS results were provided to SEER registries per their methods (npj Breast Cancer 2016). Pts diagnosed (Jan 2004 - Dec 2012) with N0 HR+ HER2- negative BC, and no prior malignancy were eligible. BCSM estimates by CT use were computed using standard cutpoints of 18 and 31 and TAILORx cutpoints of 11 and 25. Results: Among 49,681 with a RS, 9,486 (19%) had RS &lt;11, 17,988 (36%) had RS 11-17, 14,541 (29%) had RS 18-25, 3,805 (8%) had RS 26-30, and 3,861 (8%) had RS ≥31. Reported CT use and 5-y BCSM increased with increasing RS. For pts with both RS &lt;11 and RS 11-17, CT use was uncommon and 5-y BCSM was low regardless of CT use. For pts with RS 18-25, CT use was more common and the 5-y BCSM was about 1% regardless of CT use. For pts with RS of 26-30 or ≥31, CT was common, and lower 5-y BCSM was observed with CT reported yes than with CT reported no or unknown. Conclusions: Pts in real-world clinical practice with RS &lt;11, consistent with TAILORx, and pts with RS 11-17 have low 5-y BCSM with limited CT use, supporting hormonal therapy alone for pts with RS &lt;18. The high end of the TAILORx mid-range (18-25) also showed good 5-y BCSM both with and without CT, highlighting the importance of the randomized results of TAILORx. [Table: see text]

P229 - Clinical outcomes in breast cancer (BC) patients (pts) with intermediate Oncotype DX Recurrence Score (RS) results

P229 - Clinical outcomes in breast cancer (BC) patients (pts) with intermediate Oncotype DX Recurrence Score (RS) results

Abstract PD7-06: SEER study of breast cancer-specific mortality in patients with poorly differentiated tumors treated based on recurrence score results

Abstract Introduction: The SEER Program of the NCI is an authoritative source of cancer incidence and survival statistics. Linking the 21-gene assay Recurrence Score® (RS) results to the SEER Registries (N=44,825) demonstrated very low 5-year breast cancer-specific mortality (BCSM) with RS &amp;lt;18 across many key clinical-pathological subgroups, such as age, nodal status, tumor grade, and size (npj Breast Cancer. 2016;2:16017). Given the large sample size and specific interest in outcomes as a function of tumor grade, further stratification of patients with poorly differentiated tumors was performed to determine BCSM when examined by both tumor grade and tumor size. Methods: Patients were eligible if node negative (N0), HR+, HER2-negative (by RT-PCR), had no prior malignancy, had poorly differentiated (G3) tumors, and were diagnosed between Jan 2004 (test available in Jan 2004) and Dec 2011 (SEER survival updated through 2012). BCSM was defined according to pre-existing robust methodology (J Natl Cancer Inst. 2010;102:1584). RS was categorized according to the cutpoints of 18 and 31 established in the NSABP B-14 study. Five-year BCSM was estimated using actuarial methods. Results: Among 6,666 eligible patients with G3 tumors, 4,683 had tumors ≤2 cm and 1,983 had tumors &amp;gt;2 cm. Median age was 57 years; 99.1% were female. Median follow-up was 39 months. The proportion of patients with RS &amp;lt;18 was 29% among those with tumors ≤2 cm and 25% among those with tumors &amp;gt;2 cm, somewhat lower than the overall population. For RS &amp;lt;18, 5-year BCSM was 0.3% (G3; ≤2 cm) and 1.4% (G3; &amp;gt;2 cm); reported chemotherapy use was 10% and 16%, respectively. 5-year BCSM for all groups are provided in Table. An additional year of BCSM follow-up in N0 G3 disease, as well as results for patients with node positive (micrometastases or 1-3 positive nodes) G3 disease, will be available for presentation. N0, G3 tumor, RS &amp;lt;18N0, G3 tumor, RS 18-30N0, G3 tumor, RS ≥31Tumor sizeN5-y BCSM (95% CI)N5-y BCSM (95% CI)N5-y BCSM (95% CI)≤2 cm13620.3% (0.1%, 1.2%)21482.1% (1.3%, 3.3%)11732.9% (1.8%, 4.7%)&amp;gt;2 cm4861.4% (0.4%, 4.6%)8514.6% (2.7%, 7.8%)6469.0% (6.0%, 13.4%) Conclusions: Although patients with poorly differentiated tumors have worse prognosis in general, the RS identifies a sizable proportion of patients who can expect good outcomes without chemotherapy and its associated toxicity. Citation Format: Petkov VI, Miller DP, Howlader N, Baehner FL, Penberthy L, Shak S. SEER study of breast cancer-specific mortality in patients with poorly differentiated tumors treated based on recurrence score results [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-06.

Abstract P2-10-04: Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multi-center trial

Abstract Neoadjuvant systemic therapy (NST) can facilitate breast conserving surgery (BCS) for large cancers. While hormone receptor positive (HR+) cancers respond to neoadjuvant chemotherapy (NCT), pathologic complete responses (pCR) are unlikely. Neoadjuvant hormonal therapy (NHT) may make BCS possible with less toxicity than NCT. We hypothesized that the Oncotype Dx® 21-gene Recurrence Score (RS), could guide the decision to treat with NHT versus NCT to facilitate BCS. This hypothesis is based on the ability of the RS to identify ER+ patients (pts) likely to benefit from adjuvant CT vs unlikely to benefit, as well as prior studies showing that pts with a low RS have no pCRs when receiving NCT (Yardley, et al 2015). Methods: This prospective multi-center study enrolled pts with HR+, HER2-negative, invasive breast cancers not suitable for BCS (size ≥ 2 cm). Diagnosis was made by core needle biopsy (bx). Tissue blocks from the bx's were sent to Genomic Health for RS testing. Pts whose tumors had a RS &amp;lt; 11 were to receive NHT; pts with RS &amp;gt;25 tumors were to receive NCT; pts with midrange RS of 11-25 were randomized to NHT or NCT. The primary objective was the feasibility of randomizing pts with RS values 11-25 between NHT and NCT. The primary endpoint was whether 1/3 or more of randomized pts would refuse assigned treatment. Secondary endpoints included: clinical partial and complete response (cPR, cCR) rates, overall clinical response rates (CR), pCR in the breast, pCR in the breast and nodes and successful BCS. One-sample binomial test was used to compare the observed refusal rate with 1/3, along with its 95% CI. Fisher's exact test, logistic regression (for a binary endpoint), and/or ordinal regression (for an ordinal endpoint) were used to compare the 4 treatment groups for secondary endpoints. Results: Seven US and Canadian centers enrolled 64 pts; 5 were excluded (1 delay in RS result, 1 lost block, 1 HR testing discrepancy, 2 not eligible). Of 33 pts with RS 11-25, 5 (15%; 95% CI =2.9% - 27.4%) refused assignment to NCT (2 chose NHT and finished the study). This was significantly lower than the 33% target (binomial test, p=0.0292). Results for other endpoints are shown in the Table (according to treatment received); the total number of pts for the analyses is 55; 1 pt had missing data for clinical response. Results According to TreatmentTreatment GroupRS&amp;lt;11 NHTRS 11-25 NHTRS 11-25 NCTRS&amp;gt;25 NCTOverall PNN=12N=18N=11N=14 cCR8.3%22.2%36.4%28.6%0.0422cPR75%27.8%36.4%64.3% CR (cCR + cPR)83.3%50%72.7%92.9%0.0490pCR Breast8.3%6%021.4%NSpCR Breast + Nodes00014.3%NSSuccessful BCS75%72.2%63.6%57.1%NS Conclusions:This pilot showed the feasibility of using the RS to guide NST, with only a 15% refusal rate of randomly assigned treatment. Of greater interest is the finding that pts with a RS &amp;lt;11 had a high CR rate with NHT and that pts with a RS 11-25 who received NHT had a similar rate of BCS success as the pts with RS &amp;lt;11. Conversely, pts with RS&amp;gt;25 treated with NCT had the highest CR (cCR + pCR) and pCR rates. These results demonstrate that conducting a similarly designed larger trial is feasible and suggests that for pts with a low RS, NHT is a potentially effective strategy. Citation Format: Bear HD, Wan W, Robidoux A, Rubin P, Limentani S, White, Jr. RL, Granfortuna J, Hopkins JO, Oldham D, Rodriguez A, Sing AP. Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multi-center trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-10-04.

Abstract P6-07-28: The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study

Abstract BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in breast cancer (BC). The 21-gene assay test is used to estimate the risk of recurrence and to predict the benefit of adjuvant chemotherapy (ACT) at an early stage of hormone-receptor-positive (ER+) BC. This study aims to examine the implications of RecurrenceScore (RS) testing within the routine clinical practices in France. METHODS: We conducted a prospective multicentert study, with voluntary participation, involving women with ER+, HER2-, BC. Performing the assay was left at the discretionof the physicians. The final treatment decision was discussed pre and post assay among tumor board (TB). The therapeutic changes after knowledge of RS were collected. RS and classical BC prognostic markers were investigated in parallel including an estimate of the budget impact of the assay. RESULTS: 603 patients were included in this analysis (tumor size ≤ 20 mm: 70.6%; node-negative patients: 61.2%; SBR 2: 74.9%). After the first TB, ACT was recommended for 529 patients (88.0%) and hormonotherapy (HT) alone for 74 patients (12.0%). The RS was low for 59.7% of the cases, intermediate for 34.0% and high for 6.3%. Based on RS results, second TB changed treatment decision for 70.48% of patients, avoiding CT in 64 % of cases. Only 24% received ACT while 76% received HT alone. The calculated budget impact as a minimal estimate according to the French healthcare payer perspective is estimated at a savings of € 570 per patient, corresponding to a global cost-saving of € 221,730. CONCLUSION: The results of this “real life” study confirm that the 21-gene assay had a significant impact on therapeutic decision. These findings warrant further consideration for the use of this genomic assay in patients with early stage BC in France. Citation Format: Gligorov J, Dohollou N, Mouysset JL, Laplaige P, Fignon A, Lafuma A, Michaud P. The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-28.

Abstract P1-05-24: A head-to-head comparison of paraffin-embedded MammaPrnt versus oncotype DX: A Mcgill University Healh Center experience

Abstract Background: Breast cancer is the most common malignancy among women. With the introduction of improved imaging techniques and the general population's awareness of breast cancer, increasing numbers of patients are more frequently diagnosed at a very early stage. The Oncotype DX Recurrence Score (ODX) is commonly used to estimate recurrence risk and chemotherapy benefit in ER positive, node negative breast cancer. Earlier studies showed that women with Oncotype DX Recurrence score results of 11 or less had excellent outcomes which proved that thousand of patients worldwide can forgo chemotherapy and its harmful side effects based on a low Recurrence score. Now another test called the Mammaprint has been approved by the United States (US) Food and Drug Administration to assess the risk of cancer relapse. The primary study objective was to evaluate the concordance of patient results with Oncotype Dx (ODX) when compared to the 70-gene signature Mammaprint (MP), the 80-gene signature of BluePrint (BP) and TargetPrint (TP) Methods: This retrospective clinical study was carried out in the Oncology Department at the Royal Victoria Hospital (RVH), part of the MUHC. Eighty-six consecutive patient-slides node negative hormone positive breast cancer tissue tested with the Oncotype DX between October 2008 and September 2014 were included. Further inclusion criteria were age &amp;gt; 18. These same slides were then analyzed and classified with MammaPrint as low or high risk by Agendia Laboratories. BluePrint (BP) and TargetPrint (TP) analysis were also performed by Agendia Laboratories. Results: Of the 16 ODX RS between 0 and 11, 13 were low risk by MP (81 % agreement) and 16 were low risk by BP (100% agreement). Of the 50 ODX low RS cases, 33 were low risk by MP (66 % agreement) and of the 9 ODX high RS, 7 were high risk by MP (78 % agreement). Of ODX intermediate risk cases (27), 14 of were MP low risk (52 %), (48 %) 13 were MP high risk. Of BP low risk luminal tumors, 33/49 (67%) were ODX low, 14/49 (29%) ODX intermediate, and 2/49 (4%) ODX high risk. BP class was correlated with ER, PR and HER2 results. Overall agreement between clinical ER, PR, HER2 (IHC+FISH) results with TP results were 98% (81/83), 83% (69/83), 99% (82/83), and percent positive agreement for HER2 was 0/1 (of unequivocally HER2 positive cases identified correctly by TP). Conclusion: Our results show that there is a high concordance between ODX RS of 11 or less and low risk Mammaprint and Blueprint scores. When the ODX RS is above 11, our study shows that there are real differences in risk stratification between MP and ODX. At this point, there is no consensus seen when Oncotype DX is above 11. Citation Format: Desforges P, Saleh R, Nathaniel B. A head-to-head comparison of paraffin-embedded MammaPrnt versus oncotype DX: A Mcgill University Healh Center experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-24.

Abstract OT3-04-04: 21-gene recurrence score® in patients with primary metastatic ER+ HER2- breast cancer

Abstract Background and Purpose Results from the 21-gene Recurrence Score (RS) are prognostic and predictive for recurrence in early breast cancer independent of clinical-pathological parameters. Prognostic information and distribution of RS in primary metastatic breast cancer (PMBC) was reported in a previous study by King et al but remains ultimately unclear in ER+ HER2- patients. We hypothesize that there is a prognostic correlation between RS and TTP/OS in PMBCindependent of clinical-pathological parameters, and the objective of the study is to evaluate the test for that cohort. Patients and Trial Design Between 2004 and 2014, 150 patients with first diagnosis of ER+/HER2- PMBC were enrolled in a multicenter, prospectively collected database. Pretreatment breast tumor samples will be analyzed by using 21-gene RS. Minimum follow-up will be 24 months. Methods and Statistical Analysis Patient characteristics, time to first progression (TTP), overall survival (OS) and treatment modalities will be described. The association between RS risk groups and both TTP and OS will be assessed by Kaplan-Meier estimates and compared with the log-rank test. Multivariate Cox regression models will be utilized to adjust for covariates. Additionally, assessing correlation of RS results using RS cut offs of 18 and 30 and additionally of 11 and 25 as well as analysis of quantitative ER from Oncotype DX assay for patients treated first-line with endocrine therapy are planned. First results are expected to be presented in 2017. Contact information for people with a specific interest in the trial: Dr. Jana Barinoff barinoff.jana@googlemail.com. Citation Format: Barinoff J, Anastasiadou L, Brandi C, Junker-Stein A, Silbermann J, Langenfeld M, Fortmann C, Thill M. 21-gene recurrence score® in patients with primary metastatic ER+ HER2- breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-04.

Abstract PD7-05: How 21-gene recurrence score assay is being used to individualize adjuvant chemotherapy recommendations in ER+/HER2 -node positive breast cancer -A national cancer data base study

Abstract Introduction: The 21-gene Recurrence Score (RS) assay has been shown in retrospective studies to predict benefit of adjuvant chemotherapy (AC) in node positive (N+) breast cancer (BC) patients (pts). This study evaluates the trends and patterns of use of RS assay in N+, ER+/HER2-breast cancer and the impact of RS on decision to use AC in a real-world multi-institutional database. Methods: Pts with T1-T4c, N1mi-N3, ER+/HER2- BC diagnosed between 2010 and 2013, included in the National Cancer Data Base were analyzed. Pts who received neo-AC were excluded. Analyses included Cochrane-Armitage tests for trends and multivariable logistic regression assessing factors influencing RS testing and AC recommendations based on RS. Results: Among 73,049 pts, RS was obtained in 20.6%, increasing from 14.9% in 2010 to 24.4% in 2013 (p&amp;lt;0.001). RS testing was most common in N1mi (43.6%) and N1 (22.0%) and rare in N2/N3 (3.3%) BC. Of the 12,540 BC with quantitative RS results, 61.1% were low RS, 32.3% intermediate RS and 6.6% high RS. AC recommendation was less frequent in pts with RS testing compared to pts not tested (50.4% recommended AC vs 80.9%, p&amp;lt;0.001). In pts with N1mi/N1 BC, recommendation rates for AC were higher with higher RS (see table), however in N2/N3 BC, AC was recommended in the majority (71-88%) regardless of RS. Most pts (&amp;gt;85%) with RS 26-30 or high risk RS were recommended AC regardless of N stage. For pts with low risk RS, recommendation for AC increased significantly with increasing N stage (see table). On multivariable analysis, in pts with low risk RS, AC was more likely to be recommended in those with N1/N2+ stage (OR 2.3 and 9.1 vs N1mi), T2 and T3/T4 tumors (OR 1.3 and 2.2 vs T1 tumors), poorly differentiated tumors (OR 1.6) and younger age (OR 3.4 and 1.7, respectively, for &amp;lt;40 and 40-49 vs 50-59) (all p&amp;lt;0.001). Among pts with RS 18-25, AC was more likely to be recommended in those with higher tumor grade, younger age but the effect of N stage was less pronounced. Histology (IDC vs ILC) did not influence AC recommendation in any RS subset. Path N StageRS Risk GroupLow RiskIntermediate RiskHigh RiskRS&amp;lt;18RS 18-25RS 26-30RS&amp;gt;30N1mi AC No1,854 (75.9%)389 (36.9%)36 (14.6%)16 (7.0%)N1mi AC Yes590 (24.1%)666 (63.1%)210 (85.4%)212 (93.0%)N1 AC No3,000 (60.6%)699 (33.0%)75 (14.8%)33 (6.0%)N1 AC Yes1,954 (39.4%)1,422 (67.0%)431 (85.2%)518 (94.0%)N2/N3 AC No76 (29.0%)17 (16.7%)3 (12.5%)7 (14.9%)N2/N3 AC Yes186 (71.0%)85 (83.3%)21 (87.5%)40 (85.1%)p-value&amp;lt;0.001&amp;lt;0.0010.880.16 Conclusions: RS was obtained in about one fifth of pts with N+ ER+/HER2- BC, predominantly for N1mi and N1 disease. Overall, RS testing decreased frequency of recommendation of AC in N+ BC pts. The RS influenced use of AC particularly in N1mi and N1 pts, likely avoiding overtreatment of those with low risk RS and RS 18-25. Prospective data regarding RS to direct AC in N+ BC are awaited. Citation Format: Peethambaram PP, Hoskin TL, Heins CN, Habermann EB, Boughey JC. How 21-gene recurrence score assay is being used to individualize adjuvant chemotherapy recommendations in ER+/HER2 -node positive breast cancer -A national cancer data base study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-05.

Abstract P6-17-02: Evaluation of the impact of oncotype DX test results on systemic therapy in breast cancer patients at the BC cancer agency (BCCA)

Abstract Introduction: The BCCA started funding the Oncotype DX genomic test for node negative, hormone receptor positive and HER2 negative early breast cancer patients in April 2014. Individual requests for the test are reviewed and approved based on predefined BCCA specific eligibility criteria which are, any size grade 3 cancer and any grade 2 cancer over 1cm (later amended to any size) in women 80 and younger, and any grade 1 cancer in women 40 and younger. General consensus is the test result, or Recurrence Score (RS), can be used to guide whether patients should receive endocrine therapy alone (low RS[LRS] &amp;lt;18) or chemoendocrine therapy (high RS[HRS] &amp;gt;30). For patients with intermediate RS (IRS), there is no consensus on whether the benefits of chemotherapy outweigh the risks of potential toxicities. Objectives: To determine (1) the concordance of RS with treatments given to patients with LRS or HRS, (2) the treatments given to patients with IRS, and (3) the reasons for requesting the genomic test for patients outside the eligibility criteria. Methods: This was a retrospective, multi-centre analysis of breast cancer patients for whom the genomic test was requested between June 1, 2014 and May 31, 2015. Charts were reviewed to determine the RS and the therapy given following knowledge of the RS. The primary outcome was the concordance rate between LRS and receipt of endocrine therapy only, and HRS and receipt of chemoendocrine therapy. The discordance rate between RS-based recommendations and treatments given, and the type of therapy received by patients with IRS were also explored. Treatments for those with low IRS (18-24) or high IRS (25-30) were examined separately. Finally, we examined the reasons for requesting the genomic test outside eligibility criteria. Results: 435 requests were received during the study period. 395 requests were approved and test results were not found in 20 cases. Among the 375 RS results, 191 were LRS (51%), 122 were IRS (33%), and 62 were HRS (16%). The concordance rate between RS low and high and given treatments was 96%. Reasons for discordance included: patients with HRS refusing chemotherapy (n=3), patients with LRS receiving chemotherapy (n=3), patients refusing systemic treatment (n=3), and no explanation (n=1). Among the 122 patients with IRS, 81 were low-IRS and 41 were high-IRS. Overall, 27 % of patients with IRS received chemotherapy. Chemotherapy was given in 16 patients (19.7%) with low-IRS and 17 patients (41.4%) with high-IRS. The main reasons for requesting the test for patients outside eligibility criteria were: grade 1 tumors in patients older than 40 years old (n=20), node-positive disease (n=9), and grade 2 tumors less than 11 mm (n=3). Conclusion: Our results showed that the majority of patients with LRS or HRS were treated in accordance to RS-based recommendations. When treatment differed from RS-based consensus, the main reason was treatment refusal by patients. Only a quarter of patients with IRS received chemotherapy. Ongoing prospective trials will determine the utility of IRS in defining optimal therapy. Patients denied for the test were older and with grade 1 tumors, or with node-positive disease. Citation Format: Cheng V, Markarian A, de Lemos M, Schaff K. Evaluation of the impact of oncotype DX test results on systemic therapy in breast cancer patients at the BC cancer agency (BCCA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-17-02.

147PD - First prospectively-designed outcome study in estrogen receptor (ER)+ breast cancer (BC) patients (pts) with N1mi or 1-3 positive nodes in whom treatment decisions in clinical practice incorporated the 21-gene recurrence score (RS) result

147PD - First prospectively-designed outcome study in estrogen receptor (ER)+ breast cancer (BC) patients (pts) with N1mi or 1-3 positive nodes in whom treatment decisions in clinical practice incorporated the 21-gene recurrence score (RS) result

Pooled analysis of prospective European studies assessing the impact of using the 21-gene Recurrence Score assay on clinical decision making in women with oestrogen receptor–positive, human epidermal growth factor receptor 2–negative early-stage breast cancer

PurposeThe 21-gene Recurrence Score assay (Oncotype DX) provides prognostic/predictive information in oestrogen receptor positive (ER+) early breast cancer, but access/reimbursement has been limited in most European countries in the absence of prospective outcome data. Recently, two large prospective studies and a real-life 5-year outcome study have been reported. We performed a pooled analysis of prospective European impact studies to generate robust data on impact of use in different clinical subgroups. MethodsThe analysis included four studies (French, German, Spanish, and British) in ER+ human epidermal growth factor receptor 2–negative breast cancer patients (n = 527). Node-positive patients were excluded. ResultsThe analysis demonstrated that treatment recommendations changed in 32% of patients post-testing; chemotherapy recommendation rate decreased from 55% to 34%. Change rates in the individual studies ranged from 30% to 37%. The highest change rates were in patients originally recommended chemotherapy and in grade II tumours; there was no subgroup without a treatment recommendation change. Notably, 31% of patients with an intermediate Recurrence Score result had a treatment recommendation change suggesting that testing provides actionable information in this group. With the exception of the German study (where chemotherapy rates remained high [41%] post-testing), between-study variability in treatment recommendations decreased post-testing (chemotherapy: from 36–52% to 26–29%; hormonal therapy: from 48–64% to 71–74%). Physicians' confidence regarding treatment recommendations improved in all the studies after testing. ConclusionRecurrence Score testing led to changes in adjuvant chemotherapy use in approximately a third of patients, to an overall reduced chemotherapy use, and to more homogeneous decision making.

Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study.

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N=38,568). Unadjusted 5-year BCSM were 0.4% (n=21,023; 95% confidence interval (CI), 0.3–0.6%), 1.4% (n=14,494; 95% CI, 1.1–1.7%), and 4.4% (n=3,051; 95% CI, 3.4–5.6%) for Recurrence Score <18, 18–30, and ⩾31 groups, respectively (P<0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P<0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N=4,691), 5-year BCSM (unadjusted) was 1.0% (n=2,694; 95% CI, 0.5–2.0%), 2.3% (n=1,669; 95% CI, 1.3–4.1%), and 14.3% (n=328; 95% CI, 8.4–23.8%) for Recurrence Score <18, 18–30, ⩾31 groups, respectively (P<0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials.